Advancement from Small Peptide Pharmaceuticals to Orally Active Piperazine-2,5-dion-Based Cyclopeptides

Deigin, Vladislav; Linkova, Natalia; Volpina, Olga

doi:10.3390/ijms241713534

Cited by 2 publications

(1 citation statement)

References 69 publications

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“…Experimental data on Thymogen are in the scope of published data for other peptide immunomodulators. This helped us determine its application's niche in clinical practice [78,79]. Thymogen ® is registered in the Russian Ministry of Health Registration Certificate № P N002408/01 from 10.06.2009.…”

Section: Thymogenmentioning

confidence: 99%

The First Reciprocal Activities of Chiral Peptide Pharmaceuticals: Thymogen and Thymodepressin, as Examples

Deigin,

Linkova,

Vinogradova

et al. 2024

IJMS

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Peptides show high promise in the targeting and intracellular delivery of next-generation biotherapeutics. The main limitation is peptides’ susceptibility to proteolysis in biological systems. Numerous strategies have been developed to overcome this challenge by chemically enhancing the resistance to proteolysis. In nature, amino acids, except glycine, are found in L- and D-enantiomers. The change from one form to the other will change the primary structure of polypeptides and proteins and may affect their function and biological activity. Given the inherent chiral nature of biological systems and their high enantiomeric selectivity, there is rising interest in manipulating the chirality of polypeptides to enhance their biomolecular interactions. In this review, we discuss the first examples of up-and-down homeostasis regulation by two enantiomeric drugs: immunostimulant Thymogen (L-Glu-L-Trp) and immunosuppressor Thymodepressin (D-Glu(D-Trp)). This study shows the perspective of exploring chirality to remove the chiral wall between L- and D-biomolecules. The selected clinical result will be discussed.

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Section: Thymogenmentioning

confidence: 99%

The First Reciprocal Activities of Chiral Peptide Pharmaceuticals: Thymogen and Thymodepressin, as Examples

Deigin,

Linkova,

Vinogradova

et al. 2024

IJMS

Self Cite

View full text Add to dashboard Cite

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Novel Peptidomimetic Cyclo-{E(I)-E(W)}Na (CP-88) with Hematopoietic Activity Sustained in Invasive and Oral Administration: Experimental and Preclinical Evaluation

Deigin,

Vinogradova,

Vinogradov

et al. 2024

IJMS

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Over the last decades, significant progress has been made in studying agonistic and antagonistic hematopoietic peptides. The main disadvantage of this class of peptides is their low stability with noninvasive administration methods, which limits the widespread use of hematopoiesis-regulated peptide drugs in medical practice. The aim of this work is to study novel peptidomimetics with hematopoietic activity sustained in invasive and oral administration. The activity of the leading compound cyclopeptide Cyclo—[Glu(Ile)-Glu(Trp)] (CP-88) was compared to that of the pharmaceutical preparation Stemokin in stimulating the population of committed colony-forming cells in intact and irradiated mice. CP-88 peptide increases the relative number of CD34+ cells in the blood and bone marrow, leading to expanded hematopoietic stem cells. CP-88 peptide, applied 48 h before bone marrow extraction, stimulates the population of committed colony-forming cells in the normal bone marrow by 33–37% above the normal level. In recipient mice injected with irradiated bone marrow, this peptide was restored practically to normal levels of colony-forming cells in a wide range of doses at intraperitoneal and oral administration. The toxicological results conclude that in humans, considering interspecies extrapolation, the CP-88 peptide can be practically safe with a single and course administration in doses of up to 100 μg/kg. The results of this investigation underscore the significant potential of CP-88 peptide as a hematopoiesis-regulated drug and instill optimism for its future application in medical practice.

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Advancement from Small Peptide Pharmaceuticals to Orally Active Piperazine-2,5-dion-Based Cyclopeptides

Cited by 2 publications

References 69 publications

The First Reciprocal Activities of Chiral Peptide Pharmaceuticals: Thymogen and Thymodepressin, as Examples

The First Reciprocal Activities of Chiral Peptide Pharmaceuticals: Thymogen and Thymodepressin, as Examples

Novel Peptidomimetic Cyclo-{E(I)-E(W)}Na (CP-88) with Hematopoietic Activity Sustained in Invasive and Oral Administration: Experimental and Preclinical Evaluation

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